This project addresses development of novel analytical, computational and experimental methodologies to model and analyze light scattering in biological tissue. Elastic scattering is the dominant mechanism of light-tissue interaction, plays a fundamental role in all light transport processes, and has been widely employed to provide diagnostic information about tissue structure and composition. However, elastic scattering in such complex media as tissue has not been fully understood. Questions remain regarding the origins of scattering in tissue and the appropriate methods of interpreting scattering signals. Bridging this gap is the main objective of the project. We will focus on elastic light interactions for microscopy applications. This requires development of innovative computational and experimental solutions. The study will elucidate which cellular structures affect scattering signal and image formation, which morphological properties of cells can be studied optically and, equally importantly, which properties cannot be probed. In particular, the focus will be on sensing sub-diffractional, nanoscale properties of cells. We will develop a free, open-source, user-friendly finite-difference time-domain (FDTD) electromagnetic simulation software for use in biomedical light scattering applications. We will relate optical and ultrastructural properties of cells. Finally, using the computational and experimental methodologies developed in the course of the project, we will identify specific cellular origins of nanoarchitectural changes in early carcinogenesis. PUBLIC HEALTH RELEVANCE: Development of robust methods of analysis of light-tissue interaction will allow design of optical techniques for tissue diagnosis. In particular, the proposed work will facilitate development of a microscopic technique to identify some of the earliest alterations of cellular nanoarchitecture in carcinogenesis.